The effect of sodium-n-dipropyl acetate on gamma-aminobutyric acid-dependent inhibition in the rat cortex and substantia nigra in relation to its anticonvulsant activity.
1. We have examined the time course of the anticonvulsant property of valproate sodium on electroshock-induced convulsions in rats and a comparison of this has been made with the action of the drug on single unit activity in the rat brain. 2. Intraperitoneal valproate sodium (100 to 400 mg/kg) protected rats from electroshock-induced convulsion. This effect was dose-dependent, the latency of the effect decreasing as a function of dose from 5 to 2 min. 3. The time course of this anticonvulsant property was paralleled by a pronounced inhibition of the spontaneous firing rate of cortical and nigral neurones, following intraperitoneal administration of valproate sodium (100 to 400 mg/kg). 4. The inhibitory action of microiontophoretically applied gamma-aminobutyric acid (GABA) and muscimol on the firing rate of cortical neurones was potentiated within 1 to 3 min of microiontophoretic application of valproate sodium. In contrast, the inhibitory action of glycine on cortical neurones was unaffected during the microiontophoretic application of valproate sodium. 5. Microiontophoretically applied valproate sodium also potentiated inhibitory responses to GABA in rats which had received 100 mg/kg of a GABA-transaminase inhibitor, gabaculine, i.p. 16 h previously. 6. The duration of trans-synaptic inhibitory responses in the substantia nigra and cortex following submaximal electrical stimulation of the striatum and cortex respectively was, in general, unaffected by either intraperitoneal or local application of valproate sodium. 7. These observations are discussed in terms of the mechanisms underlying the rapid onset of the anticonvulsant properties of valproate sodium.
D000818:Animals; D000927:Anticonvulsants; D002540:Cerebral Cortex / Q000187:drug effects*; D004597:Electroshock; D005998:Glycine / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects*; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000927:Anticonvulsants; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D005998:Glycine